Brain Lower Grade Glioma: Mutation Analysis (MutSig v2.0)
(primary solid tumor cohort)
Maintained by Dan DiCara (Broad Institute)
Overview
Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v2.0 was used to generate the results found in this report.

  • Working with individual set: LGG-TP

  • Number of patients in set: 170

Input

The input for this pipeline is a set of individuals with the following files associated for each:

  1. An annotated .maf file describing the mutations called for the respective individual, and their properties.

  2. A .wig file that contains information about the coverage of the sample.

Summary

  • MAF used for this analysis:LGG-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 41

  • Mutations seen in COSMIC: 331

  • Significantly mutated genes in COSMIC territory: 12

  • Genes with clustered mutations (≤ 3 aa apart): 143

  • Significantly mutated genesets: 95

  • Significantly mutated genesets: (excluding sig. mutated genes):0

Mutation Preprocessing

  • Read 170 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 24649

  • After removing 12 mutations outside chr1-24: 24637

  • After removing 468 blacklisted mutations: 24169

  • After removing 446 noncoding mutations: 23723

  • After collapsing adjacent/redundant mutations: 23722

Mutation Filtering

  • Number of mutations before filtering: 23722

  • After removing 302 mutations outside gene set: 23420

  • After removing 96 mutations outside category set: 23324

  • After removing 3 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 22923

Results
Breakdown of Mutations by Type

Table 1.  Get Full Table Table representing breakdown of mutations by type.

type count
Frame_Shift_Del 441
Frame_Shift_Ins 246
In_Frame_Del 226
In_Frame_Ins 10
Missense_Mutation 15136
Nonsense_Mutation 938
Nonstop_Mutation 12
Silent 5858
Splice_Site 416
Translation_Start_Site 41
Total 23324
Breakdown of Mutation Rates by Category Type

Table 2.  Get Full Table A breakdown of mutation rates per category discovered for this individual set.

category n N rate rate_per_mb relative_rate exp_ns_s_ratio
*CpG->T 4768 274694298 0.000017 17 5 2.1
*Cp(A/C/T)->T 3403 2262327426 1.5e-06 1.5 0.43 1.7
A->G 2059 2444442244 8.4e-07 0.84 0.24 2.3
transver 4945 4981463968 9.9e-07 0.99 0.28 5
indel+null 2205 4981463968 4.4e-07 0.44 0.13 NaN
double_null 84 4981463968 1.7e-08 0.017 0.0048 NaN
Total 17464 4981463968 3.5e-06 3.5 1 3.5
Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1. 

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2.  Patients counts and rates file used to generate this plot: LGG-TP.patients.counts_and_rates.txt

CoMut Plot

Figure 3.  Get High-res Image The matrix in the center of the figure represents individual mutations in patient samples, color-coded by type of mutation, for the significantly mutated genes. The rate of synonymous and non-synonymous mutations is displayed at the top of the matrix. The barplot on the left of the matrix shows the number of mutations in each gene. The percentages represent the fraction of tumors with at least one mutation in the specified gene. The barplot to the right of the matrix displays the q-values for the most significantly mutated genes. The purple boxplots below the matrix (only displayed if required columns are present in the provided MAF) represent the distributions of allelic fractions observed in each sample. The plot at the bottom represents the base substitution distribution of individual samples, using the same categories that were used to calculate significance.

Significantly Mutated Genes

Column Descriptions:

  • N = number of sequenced bases in this gene across the individual set

  • n = number of (nonsilent) mutations in this gene across the individual set

  • npat = number of patients (individuals) with at least one nonsilent mutation

  • nsite = number of unique sites having a non-silent mutation

  • nsil = number of silent mutations in this gene across the individual set

  • n1 = number of nonsilent mutations of type: *CpG->T

  • n2 = number of nonsilent mutations of type: *Cp(A/C/T)->T

  • n3 = number of nonsilent mutations of type: A->G

  • n4 = number of nonsilent mutations of type: transver

  • n5 = number of nonsilent mutations of type: indel+null

  • n6 = number of nonsilent mutations of type: double_null

  • p_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene

  • p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene

  • p_cons = p-value for enrichment of mutations at evolutionarily most-conserved sites in gene

  • p_joint = p-value for clustering + conservation

  • p = p-value (overall)

  • q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 41. Number of genes displayed: 35. Click on a gene name to display its stick figure depicting the distribution of mutations and mutation types across the chosen gene (this feature may not be available for all significant genes).

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_classic p_ns_s p_cons p_joint p q
1 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 216008 131 131 2 0 123 0 0 8 0 0 <1.00e-15 1.6e-15 NaN NaN <1.00e-15 <1.20e-11
2 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 1280217 78 73 70 2 2 3 6 6 58 3 1.33e-15 0.0024 NaN NaN 1.33e-15 1.20e-11
3 CIC capicua homolog (Drosophila) 702843 40 35 34 0 15 1 1 5 18 0 2.11e-15 0.00012 NaN NaN 2.11e-15 1.27e-11
4 TP53 tumor protein p53 209503 113 88 63 2 46 12 14 25 13 3 3.00e-15 1.1e-11 NaN NaN 3.00e-15 1.36e-11
5 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 558011 15 15 10 0 0 5 5 2 3 0 8.22e-15 0.014 NaN NaN 8.22e-15 2.64e-11
6 FUBP1 far upstream element (FUSE) binding protein 1 335021 19 19 18 2 0 0 1 2 16 0 8.77e-15 0.66 NaN NaN 8.77e-15 2.64e-11
7 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 401699 13 12 11 1 1 2 3 0 7 0 1.18e-13 0.26 NaN NaN 1.18e-13 3.06e-10
8 NOTCH1 Notch homolog 1, translocation-associated (Drosophila) 1034775 23 16 20 2 4 3 1 6 7 2 1.58e-10 0.029 NaN NaN 1.58e-10 3.58e-07
9 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 206544 8 8 8 0 1 1 0 3 3 0 2.93e-10 0.25 NaN NaN 2.93e-10 5.89e-07
10 ARID1A AT rich interactive domain 1A (SWI-like) 986587 13 11 13 0 1 0 0 1 10 1 3.35e-08 0.077 NaN NaN 3.35e-08 6.05e-05
11 TIMD4 T-cell immunoglobulin and mucin domain containing 4 199368 6 6 3 1 0 1 0 1 4 0 4.11e-08 0.82 NaN NaN 4.11e-08 6.76e-05
12 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 1473142 14 11 14 1 1 2 1 2 3 5 5.77e-08 0.096 NaN NaN 5.77e-08 8.69e-05
13 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 198137 6 6 2 0 0 4 0 2 0 0 6.51e-08 0.058 NaN NaN 6.51e-08 9.06e-05
14 ZNF844 zinc finger protein 844 212375 6 5 2 0 0 0 2 4 0 0 1.02e-06 0.23 NaN NaN 1.02e-06 0.00132
15 IL32 interleukin 32 87796 4 4 1 0 0 0 0 0 4 0 1.28e-06 1 NaN NaN 1.28e-06 0.00155
16 TCF12 transcription factor 12 (HTF4, helix-loop-helix transcription factors 4) 385695 6 6 5 0 0 0 0 0 6 0 1.83e-06 0.75 NaN NaN 1.83e-06 0.00204
17 ZBTB20 zinc finger and BTB domain containing 20 345917 7 7 7 1 1 0 3 1 2 0 1.92e-06 0.5 NaN NaN 1.92e-06 0.00204
18 MUC7 mucin 7, secreted 194133 8 5 7 0 1 2 5 0 0 0 4.66e-06 0.018 NaN NaN 4.66e-06 0.00469
19 ZNF57 zinc finger protein 57 284991 7 6 4 0 1 1 1 4 0 0 8.97e-06 0.16 NaN NaN 8.97e-06 0.00854
20 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 669290 10 8 8 0 1 2 0 6 1 0 2.15e-05 0.08 NaN NaN 2.15e-05 0.0194
21 PRAMEF11 PRAME family member 11 208592 6 5 6 1 0 2 2 2 0 0 2.55e-05 0.4 NaN NaN 2.55e-05 0.0220
22 ANKRD30A ankyrin repeat domain 30A 634412 7 7 5 2 2 0 0 5 0 0 2.92e-05 0.56 NaN NaN 2.92e-05 0.0240
23 ZNF91 zinc finger protein 91 598251 5 5 4 1 2 1 2 0 0 0 3.15e-05 0.4 NaN NaN 3.15e-05 0.0247
24 ZNF845 zinc finger protein 845 472789 6 6 4 1 0 3 2 1 0 0 3.85e-05 0.32 NaN NaN 3.85e-05 0.0290
25 SPDYE5 speedy homolog E5 (Xenopus laevis) 144980 4 4 3 0 3 0 1 0 0 0 4.19e-05 0.38 NaN NaN 4.19e-05 0.0303
26 TPTE transmembrane phosphatase with tensin homology 295452 7 6 7 2 0 0 1 3 3 0 4.46e-05 0.76 NaN NaN 4.46e-05 0.0310
27 C9orf79 chromosome 9 open reading frame 79 713528 8 7 8 0 2 3 1 1 1 0 5.54e-05 0.06 NaN NaN 5.54e-05 0.0371
28 OR5A1 olfactory receptor, family 5, subfamily A, member 1 161840 4 4 4 0 1 1 1 1 0 0 7.04e-05 0.22 NaN NaN 7.04e-05 0.0455
29 NOX4 NADPH oxidase 4 305569 6 5 3 0 0 1 1 0 4 0 9.77e-05 0.45 NaN NaN 9.77e-05 0.0610
30 DDX5 DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 320234 5 5 4 0 0 2 0 1 2 0 0.000103 0.46 NaN NaN 0.000103 0.0618
31 PSD3 pleckstrin and Sec7 domain containing 3 548440 6 6 6 0 0 1 4 0 1 0 0.000118 0.1 NaN NaN 0.000118 0.0689
32 KLKB1 kallikrein B, plasma (Fletcher factor) 1 334402 5 5 5 0 2 1 1 1 0 0 0.000148 0.21 NaN NaN 0.000148 0.0836
33 OR4A16 olfactory receptor, family 4, subfamily A, member 16 167440 4 4 4 0 0 1 1 1 1 0 0.000161 0.36 NaN NaN 0.000161 0.0858
34 CYP2C19 cytochrome P450, family 2, subfamily C, polypeptide 19 256162 4 4 4 0 2 1 0 0 1 0 0.000161 0.32 NaN NaN 0.000161 0.0858
35 RPTN repetin 401710 6 5 6 1 2 1 0 1 2 0 0.000168 0.58 NaN NaN 0.000168 0.0868
IDH1

Figure S1.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

ATRX

Figure S2.  This figure depicts the distribution of mutations and mutation types across the ATRX significant gene.

CIC

Figure S3.  This figure depicts the distribution of mutations and mutation types across the CIC significant gene.

TP53

Figure S4.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

PIK3CA

Figure S5.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

FUBP1

Figure S6.  This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

PIK3R1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

NOTCH1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

PTEN

Figure S9.  This figure depicts the distribution of mutations and mutation types across the PTEN significant gene.

ARID1A

Figure S10.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

TIMD4

Figure S11.  This figure depicts the distribution of mutations and mutation types across the TIMD4 significant gene.

NF1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

IDH2

Figure S13.  This figure depicts the distribution of mutations and mutation types across the IDH2 significant gene.

ZNF844

Figure S14.  This figure depicts the distribution of mutations and mutation types across the ZNF844 significant gene.

IL32

Figure S15.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

TCF12

Figure S16.  This figure depicts the distribution of mutations and mutation types across the TCF12 significant gene.

ZBTB20

Figure S17.  This figure depicts the distribution of mutations and mutation types across the ZBTB20 significant gene.

MUC7

Figure S18.  This figure depicts the distribution of mutations and mutation types across the MUC7 significant gene.

ZNF57

Figure S19.  This figure depicts the distribution of mutations and mutation types across the ZNF57 significant gene.

EGFR

Figure S20.  This figure depicts the distribution of mutations and mutation types across the EGFR significant gene.

PRAMEF11

Figure S21.  This figure depicts the distribution of mutations and mutation types across the PRAMEF11 significant gene.

ANKRD30A

Figure S22.  This figure depicts the distribution of mutations and mutation types across the ANKRD30A significant gene.

ZNF91

Figure S23.  This figure depicts the distribution of mutations and mutation types across the ZNF91 significant gene.

ZNF845

Figure S24.  This figure depicts the distribution of mutations and mutation types across the ZNF845 significant gene.

SPDYE5

Figure S25.  This figure depicts the distribution of mutations and mutation types across the SPDYE5 significant gene.

TPTE

Figure S26.  This figure depicts the distribution of mutations and mutation types across the TPTE significant gene.

C9orf79

Figure S27.  This figure depicts the distribution of mutations and mutation types across the C9orf79 significant gene.

OR5A1

Figure S28.  This figure depicts the distribution of mutations and mutation types across the OR5A1 significant gene.

NOX4

Figure S29.  This figure depicts the distribution of mutations and mutation types across the NOX4 significant gene.

DDX5

Figure S30.  This figure depicts the distribution of mutations and mutation types across the DDX5 significant gene.

PSD3

Figure S31.  This figure depicts the distribution of mutations and mutation types across the PSD3 significant gene.

OR4A16

Figure S32.  This figure depicts the distribution of mutations and mutation types across the OR4A16 significant gene.

CYP2C19

Figure S33.  This figure depicts the distribution of mutations and mutation types across the CYP2C19 significant gene.

COSMIC analyses

In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.

Table 4.  Get Full Table Significantly mutated genes (COSMIC territory only). To access the database please go to: COSMIC. Number of significant genes found: 12. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 131 5 131 850 195452 3.1e-14 8.4e-11
2 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 6 6 6 1020 498 3.7e-14 8.4e-11
3 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 13 33 6 5610 12 2.8e-13 4.2e-10
4 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 15 220 13 37400 1923 1.2e-12 1.4e-09
5 TP53 tumor protein p53 113 356 111 60520 42165 1.8e-12 1.6e-09
6 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 8 767 8 130390 503 3.2e-08 0.000022
7 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 10 293 6 49810 59 3.4e-08 0.000022
8 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 10 30 3 5100 1 9.4e-07 0.00047
9 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 14 285 5 48450 7 1e-06 0.00047
10 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 4 32 3 5440 60 1.1e-06 0.00047

Note:

n - number of (nonsilent) mutations in this gene across the individual set.

cos = number of unique mutated sites in this gene in COSMIC

n_cos = overlap between n and cos.

N_cos = number of individuals times cos.

cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene.

p = p-value for seeing the observed amount of overlap in this gene)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Clustered Mutations

Table 5.  Get Full Table Genes with Clustered Mutations

num gene desc n mindist nmuts0 nmuts3 nmuts12 npairs0 npairs3 npairs12
3643 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 131 0 8515 8515 8515 8515 8515 8515
8201 TP53 tumor protein p53 113 0 476 660 1123 476 660 1123
3644 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 6 0 15 15 15 15 15 15
1672 CIC capicua homolog (Drosophila) 40 0 14 22 42 14 22 42
683 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 78 0 13 17 22 13 17 22
9188 ZNF844 zinc finger protein 844 6 0 7 7 15 7 7 15
9083 ZNF57 zinc finger protein 57 7 0 6 6 14 6 6 14
2463 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 10 0 4 4 4 4 4 4
5967 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 15 0 3 5 6 3 5 6
402 ANKRD30A ankyrin repeat domain 30A 7 0 3 3 3 3 3 3

Note:

n - number of mutations in this gene in the individual set.

mindist - distance (in aa) between closest pair of mutations in this gene

npairs3 - how many pairs of mutations are within 3 aa of each other.

npairs12 - how many pairs of mutations are within 12 aa of each other.

Geneset Analyses

Table 6.  Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 95. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_ns_s p q
1 HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE Genes involved in reductive carboxylate cycle (CO2 fixation) ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2 11 ACLY(3), ACO1(2), ACO2(2), ACSS1(1), ACSS2(3), FH(1), IDH1(131), IDH2(6) 3363648 149 140 16 0 128 6 0 13 2 0 2.33e-15 <1.00e-15 <8.80e-14
2 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(2), ACO2(2), FH(1), IDH1(131), IDH2(6) 2251788 142 138 9 0 126 5 0 11 0 0 1.11e-15 <1.00e-15 <8.80e-14
3 TELPATHWAY Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 15 AKT1(1), EGFR(10), IGF1R(3), POLR2A(3), PPP2CA(3), PRKCA(3), RB1(4), TEP1(5), TERF1(1), TP53(113), XRCC5(1) 7123118 147 99 95 6 54 16 19 36 18 4 8.82e-14 <1.00e-15 <8.80e-14
4 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 16 APAF1(1), ATM(4), BAX(1), CCND1(1), CDK2(1), CDK4(1), E2F1(1), MDM2(2), RB1(4), TIMP3(2), TP53(113) 4580868 131 92 81 6 49 14 19 29 17 3 9.58e-11 <1.00e-15 <8.80e-14
5 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 12 ATM(4), CDC25A(1), CDK2(1), CDK4(1), CHEK1(2), MYT1(2), RB1(4), TP53(113), WEE1(1) 4452968 129 91 79 9 49 14 17 27 19 3 6.69e-08 <1.00e-15 <8.80e-14
6 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 7 MAX(4), SP3(2), TP53(113), WT1(1) 1784759 120 91 69 2 49 13 14 28 13 3 6.55e-15 <1.00e-15 <8.80e-14
7 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 7 ATM(4), ATR(4), CHEK1(2), CHEK2(3), TP53(113) 4056688 126 88 76 6 50 16 15 28 14 3 2.04e-08 <1.00e-15 <8.80e-14
8 G1_TO_S_CELL_CYCLE_REACTOME ATM, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG2, CCNH, CDC25A, CDC45L, CDK2, CDK4, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CREB3, CREB3L1, CREB3L3, CREB3L4, CREBL1, CREBL1, TNXB, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, FLJ14001, GADD45A, GBA2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MNAT1, MYC, MYT1, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA2, POLE, POLE2, PRIM1, PRIM2A, RB1, RBL1, RPA1, RPA2, RPA3, TFDP1, TFDP2, TP53, WEE1 64 ATM(4), CCNA1(1), CCND1(1), CCNE2(1), CCNG2(1), CCNH(2), CDC25A(1), CDK2(1), CDK4(1), CDKN1B(1), CDKN2A(2), CDKN2C(1), CREB3L1(1), E2F1(1), E2F3(1), E2F5(1), GBA2(1), MCM3(2), MCM4(3), MCM5(1), MCM6(1), MCM7(2), MDM2(2), MYT1(2), ORC1L(2), ORC2L(1), ORC3L(1), ORC4L(1), POLE(6), PRIM1(1), RB1(4), RBL1(2), RPA1(2), TNXB(9), TP53(113), WEE1(1) 19490078 178 96 128 22 61 20 24 44 26 3 4.78e-08 1.22e-15 9.33e-14
9 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(2), ACO2(2), FH(1), IDH1(131), IDH2(6), IDH3B(1), PC(1), PCK1(3), SUCLG2(1) 5210151 148 138 15 2 128 8 0 12 0 0 3.00e-15 1.67e-15 9.33e-14
10 HSA04210_APOPTOSIS Genes involved in apoptosis AIFM1, AKT1, AKT2, AKT3, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CAPN1, CAPN2, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHP, CHUK, CSF2RB, CYCS, DFFA, DFFB, ENDOG, FADD, FAS, FASLG, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1RAP, IL3, IL3RA, IRAK1, IRAK2, IRAK3, IRAK4, MAP3K14, MYD88, NFKB1, NFKB2, NFKBIA, NGFB, NTRK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, RIPK1, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFSF10, TP53, TRADD, TRAF2 80 AIFM1(2), AKT1(1), APAF1(1), ATM(4), BAX(1), BIRC2(1), CFLAR(1), CYCS(2), DFFA(1), FAS(1), IL1B(1), IL1R1(1), IL1RAP(1), IL3RA(2), IRAK2(1), IRAK3(4), IRAK4(1), MAP3K14(1), NFKB1(1), NFKB2(1), PIK3CA(15), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(13), PIK3R2(1), PIK3R3(1), PIK3R5(1), PPP3CA(1), PPP3CC(1), PPP3R2(1), PRKAR1A(1), RELA(1), RIPK1(1), TNFRSF10D(1), TP53(113) 21116382 186 109 129 28 57 27 27 42 30 3 5.36e-06 1.67e-15 9.33e-14

Table 7.  Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 0. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_ns_s p q
1 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 9 GABRA1(7), GABRA3(1), GABRA4(3), GABRA5(1), GABRA6(3) 1995807 15 9 15 4 3 4 1 5 2 0 0.36 0.007 1
2 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 12 CDK2(1), CDKN1B(1), CUL1(1), E2F1(1), RB1(4), SKP2(2), UBE2M(1) 2167354 11 8 11 1 1 1 4 1 4 0 0.17 0.0082 1
3 SKP2E2FPATHWAY E2F-1, a transcription factor that promotes the G1/S transition, is repressed by Rb and activated by cdk2/cyclin E. CCNA1, CCNE1, CDC34, CDK2, CUL1, E2F1, RB1, SKP1A, SKP2, TFDP1 9 CCNA1(1), CDC34(1), CDK2(1), CUL1(1), E2F1(1), RB1(4), SKP2(2) 2161111 11 8 11 1 1 1 4 1 4 0 0.19 0.01 1
4 UREACYCLEPATHWAY Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 6 ASL(2), CPS1(4), GLS(1), GLUD1(3), GOT1(2) 1974792 12 6 12 2 1 2 0 5 4 0 0.44 0.028 1
5 HSA00592_ALPHA_LINOLENIC_ACID_METABOLISM Genes involved in alpha-Linolenic acid metabolism ACOX1, ACOX3, FADS2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6 15 ACOX1(2), ACOX3(3), FADS2(2), PLA2G2D(1), PLA2G3(3), PLA2G4A(2), PLA2G5(1), PLA2G6(2) 2562807 16 7 16 2 3 4 2 5 2 0 0.11 0.031 1
6 PLCPATHWAY Phospholipase C hydrolyzes the membrane lipid PIP2 to DAG, which activates protein kinase C, and IP3, which causes calcium influx. AKT1, PIK3CA, PIK3R1, PLCB1, PLCG1, PRKCA, PRKCB1, VAV1 5 AKT1(1), PLCB1(2), PLCG1(6), PRKCA(3), VAV1(3) 2289050 15 10 14 3 4 3 2 4 1 1 0.26 0.034 1
7 MALATEXPATHWAY The tricarboxylate transfer pathway shuttles acetyl groups of acetyl-CoA between mitochondria and the cytoplasm. ACLY, CS, MDH1, ME1, PC, PDHA1, SLC25A1, SLC25A11 8 ACLY(3), ME1(1), PC(1), PDHA1(2), SLC25A1(1) 2347660 8 7 8 0 1 2 0 3 2 0 0.068 0.041 1
8 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(2), DCN(1), FMOD(1), LUM(2) 917147 6 5 6 2 1 1 0 4 0 0 0.69 0.054 1
9 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(1), NAT1(1), NAT2(2), XDH(7) 2013925 11 6 11 0 3 1 0 5 2 0 0.052 0.055 1
10 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 ACHE(2), CHAT(3), PDHA1(2), PDHA2(4) 1756754 11 6 11 1 2 5 1 1 2 0 0.048 0.058 1
Methods & Data
Methods

In brief, we tabulate the number of mutations and the number of covered bases for each gene. The counts are broken down by mutation context category: four context categories that are discovered by MutSig, and one for indel and 'null' mutations, which include indels, nonsense mutations, splice-site mutations, and non-stop (read-through) mutations. For each gene, we calculate the probability of seeing the observed constellation of mutations, i.e. the product P1 x P2 x ... x Pm, or a more extreme one, given the background mutation rates calculated across the dataset. [1]

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
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